Anti-sense technologies hold tremendous promise for the treatment of a wide range of disease that include cancer, infectious diseases and dominant genetic disorders. Despite the tremendous promise of this approach, there have been few clear successes. In order for anti- sense therapy to reach the bedside there has to be progress in several areas that include improved polynucleotide transfer (e.g. liposomes, catinoic lipids) and increased destruction or inhibition of the targeted sense sequence. The work within this proposal will address the latter area by developing a new method for destroying the targeted nucleic acid using a novel and innovative chemical nuclease. The previously-developed chemical nucleases cannot be used in mammalian cells since they are toxic and require strong reducing agents not available in living cells. Using our intricate and extensive knowledge of mechanisms of action of redox active compounds, we have designed several molecules that should be highly-specific nucleases active in living cells and with several molecules that should be highly-specific nucleases active in living cells and with several advantageous properties. They have low toxicity, can be recycled so as to cut nucleic acids in a catalytic fashion and utilize reducing agents that are plentiful and endogenous to mammalian cells. The practical outcome of developing such class of reagents will be a new family of drugs with enhanced efficacy against a wide spectrum of diseases. PROPOSED COMMERCIAL APPLICATION: The new method of antisense gene therapy will be commercialized by: 1) licensing the technology for cancer gene therapies to pharmaceutical companies, 2) licensing the technology for therapy against infectious diseases, 3) licensing the technology for therapy against dominant genetic disorders, 4) sell the technology in the form of kits to biomedical researchers.